With the advent of hydrophilic or soft contact lenses, following the successful experiments of Wichterle and Seiderman reported in U.S. Pat. Nos. 2,979,576 and 3,721,657, respectively, the practitioner was given another means to correct visual impairments in his patient population. The main virtues of these lenses were their ease of manufacture, their complete transparency and their increased comfort to the user when compared with hard plastic lenses developed much earlier.
The earliest soft lenses offered commercially in the 1970's were made from polar monomers, e.g., hydroxyethylmethacrylate (HEMA), polymethylmethacrylate (PMMA), or polyvinylpyrrolidone (PVP) polymeric materials having the appearance of soft, transparent hydrogels. Within the past several years, however, other materials such as various silicone based polymers have become available and used for the manufacture of soft lenses.
The increased comfort experienced by the user which has resulted in near universal acceptance of soft contact lenses is brought about by the ability of the lens to absorb water. These lenses, when viewed under high power microscopy, appear as a highly porous matrix. When the lens is swelled in aqueous solutions prior to its initial use by the patient, this polar matrix allows the lens to absorb large quantities of water, in excess of 100 per cent of the weight of the dry lens. Consequently when placed on the eye, the user does not experience the discomfort of the foreign object in the eye but rather experiences the somewhat cooling sensation of the additional fluid being added to the eye.
The water-compatible properties which provide user comfort also are the basis for binding of exogenous materials, leading to formation of deposits on the anterior (air-exposed) surface of the lens. Deposit buildup may be exacerbated by conventional aseptization methods, with hazing of vision, loss of optical acuity, and moderate to severe eye irritation. Deposit formation is a primary cause of dissatisfaction by roughly 1/3 of the lens wearing population to adapt successfully to soft contact lenses. These statistics also make it clear that currently available cleaning methods are inadequate for dealing with problems experienced by patients classified as "heavy" depositors.
In the early 1970's it was first demonstrated that deposits on hydrophilic lenses contained proteins found in the normal human tear fluid. These data were summarized in a 1982 review article by F. C. Wedler & T. Riedhammer, "Soft Contact Lenses: Formation of Deposits," [in CRC Critical Reviews on Biocompatibility, Vol. II, chapter 3, pp. 31-46, CRC Press, Boca Raton, Fla. ] the disclosure of which is hereby incorporated by reference. These findings also refuted the belief that these deposits were bacterial plaques which would, if the "contaminated" lens were not replaced, cause infection and damage to the eye.
Until fairly recently, methods for separation, purification, detection, and quantification of sub-microgram levels of bio-materials obtained from soft contact lenses did not exist. In 1987, biochemical techniques were developed for quantitative analysis of biomaterials deposited on single patients lenses [F. C. Wedler, D. Horensky, B. L. Illman & M. Mowrey-Mckee, "Analysis of protein and mucin components deposited on a hydrophilic contact lenses", Clin. Exptl. Optom., 70: 59-68]. Substantial amounts of tear fluid proteins were detected on "normal" patient lenses with which hazing and eye irritation were not observed. The four major tear fluid proteins detected in these studies were albumin, lysozyme, lactoferrin, and pre-albumin. The most important discovery arising from this works was that "heavy lens deposits did not correlate with deposition of tear fluid proteins, but did coordinate strongly with mucin, a heterogeneous mixture of derivatized polysaccharides.
Prior to this finding, it was believed that proteinaceous materials were the main cause of irritating lens deposits, and based on this, protein-degrading enzymes (proteases) were used in cleaning solutions to remove these irritating deposits. Indeed, U.S. Pat. No. 3,910,296 discloses and claims the use of protease-containing solutions for soft contact lens cleaning. Included in this formulation were sulfhydryl-group containing compounds, needed to activate the protease (papain) and which could also reduce disulfide bonds in the protein substrate, but which have an offensive "rotten egg" odor.
A number of subsequent disclosures have sought to improve on the basic concept of protease-based cleaners. These additional disclosures suggest that other substituents be added to the cleaning solution, that the condition under which cleaning occurs be adjusted, or both. For example, U.S. Pat. No. 4,096,870 suggests the use of the digestive aid pancreatin, a crude mixture of hydrolytic enzymes extracted from hog pancreas, formulated in combination with boric acid and sodium chloride as a cleaning mixture. U.S. Pat. No. 4,285,738 suggest the use of a hypertonic solution of urea and/or a guanidine salt added to the protease formulation along with a sulfhydryl compound or other suitable reducing reagent capable of cleaning disulfide bonds.
Commercially available products for enzymatic cleaning of soft(hydrophilic) contact lenses include, for example, OPTI-ZYME.TM. (Alcon Laboratories) based on porcine pancreatin as the active ingredient, and ALLERGAN ENZYMATIC.TM., EXTENZYME.TM., and PROFREE/GP.TM. (Allergan Pharmaceuticals) based on papain.
Now that the major cause of extraneous heavy lens deposits is known to be mucin, not proteins, it becomes clear why the majority of currently available commercial enzyme-based cleaners fail to remove heavy deposits. Although the enzymes contained in these cleaners will specifically attack and degrade proteinaceous materials, they are ineffective against mucin, which is a heterogeneous mixture of complex carbohydrates (mucopolysaccharides) and carbohydrate surrounding a protein core (glycoproteins).
Since presently available enzyme-based cleaning solutions fail to degrade or remove mucin deposits from soft contact lenses, there is obviously a need to develop a new, second-generation cleaner, based on mucin-degrading enzymes. These mucin degrading enzymes could be used either alone or in combination with proteases to enhance the cleaning of heavily deposited hydrophilic lenses.